Diabetes has been described as a ‘silent pandemic’, with the World Health Organization stating that 537 million people globally are living with diabetes in 2021 (Mnif et al, 2022). It is suggested that it is of a bigger concern in developing economies like India, mainly driven by the increasing prevalence of overweight and obesity, and unhealthy lifestyles (Pradeepa and Mohan, 2021). In India, there were 101 million people living with diabetes and 136 million people with prediabetes in 2021, suggesting that the prevalence of diabetes in the country is considerably higher than previously estimated (Anjana et al, 2023). The limitations and impairments associated with diabetes include vascular, neurological, cardiac and renal impairments. However late diagnosis, failure to meet treatment objectives and non-adherence to treatment can lead to severe complications such as nephropathy, neuropathy, retinopathy, amputations and stroke (Oyewole et al, 2023).
Worryingly, diabetes-related ulcers (DRUs) are very prevalent, with a 6.3% global prevalence among adults with diabetes, equating to approximately 33 million people (McDermott et al, 2023). Ghosh and Valia (2017) estimate that, in India, 25% of people with diabetes develop DRUs, of which 50% become infected, requiring hospitalisation, while 20% need amputation, with DRUs contributing to approximately 80% of all non-traumatic amputations in the country.
Slough and prolonged inflammatory process in DRUs
An integral part of wound management and wound bed preparation involves debridement, which is defined as the removal of non-viable wound components, including necrotic material, slough and biofilm. This can be sometimes achieved by autolytic or mechanical methods (Eriksson et al, 2022). Slough is a common feature of non-healing wounds (Townsend et al, 2024), and is a major barrier to wound progression (Angel, 2019). It contributes to delayed wound healing by prolonging the inflammatory response, which results in high levels of protease and pro-inflammatory cytokine production inflammation (Angel, 2019; McGuire et al, 2019). Slough also attracts microorganisms to the wound site (Percival and Sulaiman, 2015). Bacteria can form biofilm in wound slough, which further delays and complicates wound healing (Percival and Sulaiman, 2015).
Consequently, desloughing is a necessary procedure to improve the wound healing process and is deemed a lower-risk alternative to debridement, using wound cleansing agents and wound care products (Angel, 2019).Evidence suggests that slough-trapping fibre dressings remove of slough and can reduce treatment costs, improve patient outcomes and maintain patient safety by preventing further complications (Grothier, 2015).
Moreover, in DRUs, there is an increase in matrix metalloproteinases (MMPs) and a down-regulation of their inhibitors (tissue inhibitors of metalloproteinases; Chakraborty et al, 2022). In this proteolytic environment, DRUs fail to heal due to a reduction in extracellular matrix formation, matrix degradation, delayed cell migration and inhibition of collagen deposition (Chakraborty et al, 2022). Treatments that enhance DRU healing are often associated with reducing inflammatory process in the diabetic wound environment (Andrews et al, 2015). Considering the damaging role of high levels of MMPs in complicated wounds, dressings that reduce these proteinases may support the healing process (Dissemond et al, 2020a).
In view of this, the authors sought a local treatment protocol that would sequentially provide desloughing of the wound, management of local infection, as well as reduce the inflammatory process, to hasten wound closure.
Polyabsorbent fibres dressings with technology lipido-colloid and technology lipido-colloid silver
The polyabsorbent fibres dressing pad (UrgoClean®, Laboratoires Urgo) supports the absorption of wound exudate as well as the trapping of sloughy residue (Meaume et al, 2012b; Sigal et al, 2019) and is considered to offer a safe and effective method to remove debris from the wound bed (Milne, 2015). The desloughing properties of the polyabsorbent fibre dressings have been demonstrated to be significantly superior to that of hydrofibre dressings in a European randomised controlled trial involving 159 patients (Meaume et al, 2014). A non-controlled open-label prospective, multicentre clinical trial has also reported wound area reduction associated with effective and rapid desloughing of the wound bed tissue with these fibres (all venous leg ulcers and pressure ulcers treated were debrided by week 3; Meaume et al, 2012b).
The polyabsorbent pad is coated with a soft-adherent lipido-colloid layer (TLC) that promotes healing and enables atraumatic removal (Trudigan et al, 2014). To provide an antimicrobial effect, silver sulfate is included in the TLC matrix to produce polyabsorbent fibre dressings – the TLC-Ag dressing (UrgoClean Ag®, Laboratoires Urgo). The controlled supply of Ag+ at the surface into the lipido-colloid gel, provides a constant antimicrobial activity strictly in contact with the wound (Adolphus et al, 2015).
This combination has been shown to possess an antibiofilm action, as reported by an in vitro study conducted with biofilms of Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Desroche et al, 2016). The results show a significant decrease of the biofilm population by a log reduction of 4.6 after 24 hours of exposure, which was maintained for 7 days, with reduction values up to 4 log (reduction of biofilm superior to 99.99%). The combined action of polyabsorbent fibres and TLC-Ag matrix of this polyabsorbent silver dressing has been shown to enable a more rapid disruption of in vitro biofilms when compared to carboxymethylcellulose dressing, which combines ionic silver, a metal chelating agent, and a surfactant (Hydrofiber Ag + Extra; Desroche et al, 2017).
A prospective, multicentre, non-comparative clinical trial was also conducted with this silver dressing in patients with wounds at high-risk of infection (Dalac et al, 2016). Over a maximum period of 4 weeks of treatment, wound surface area, mostly covered by sloughy tissue, was reduced by 32.5%, and 54.1% of wounds were debrided (defined by <30% of sloughy tissue covering the wound bed). In a multicentre study of 2,270 patients with exuding wounds of different aetiology at risk of infection or with clinical signs of local infection, an improvement in healing process was reported after a mean duration of treatment of 22 ± 13 days n 90.6% of cases, along with a reduction in all clinical signs of local infection, regardless of exudate level and proportion of sloughy tissues in the wound bed at baseline (Dissemond et al, 2020a).
TLC-nano-oligosaccharide factor (sucrose octasulfate) dressings
The TLC-nano-oligosaccharide factor (TLC-NOSF)/sucrose octasulfate dressing has MMP-reducing properties and has been shown in literature to promote healing in various types of chronic wounds (Munter et al 2017; Edmonds et al 2018).
In a 2021 systematic review of TLC-NOSF dressings (UrgoStart® Treatment Range, Laboratoires Urgo, France), 21 clinical studies assessing these dressings were identified, ranging from double-blind randomised control trials (RCTs) to real-life series, involving more than 12,000 patients. The authors showed that TLC-NOSF dressings are an evidence-based solution for the management of chronic wounds, enhancing wound healing, reducing healing times, and increasing patients’ health-related quality of life, while being a cost-effective, and even cost-saving, treatment (Nair et al, 2021).
TLC-NOSF dressings are currently recommended by several guidelines, including the International Working Group on the Diabetic Foot (2023), the UK’s National Institute for Health and Care Excellence (2023) and Diabetes Feet Australia (2021).
Sequential treatment
Interestingly, the report of two cases with complex DRUs has highlighted the potential benefits of a sequential treatment with the polyabsorbent fibres with TLC-Ag dressings followed by TLC-NOSF dressings (Galea and Khatib, 2020). Dowsett (2023) also presented two venous leg ulcer cases that were initially managed with the polyabsorbent fibres dressings coated with TLC-Ag for 6 weeks and 9 weeks respectively to manage infection and biofilm, and then continued with a TLC-NOSF dressing for wound closure and improvement in patient outcomes.
Wong et al (2023) presented a prospective cohort study with 28 patients included in the final analysis on patients with venous leg ulcers who received sequential therapy, consisting of 2 weeks of a polyabsorbent fibre with TLC-Ag dressing followed by TLC-NOSF dressings and a two-layer compression bandage, until complete wound healing. Median time to wound healing was 10 weeks, and 57.1% of patients achieved complete wound closure at 3 months. There was significant wound area reduction after 1 month (mean area decreased from 8.44 cm2 to 5.81 cm2, 31.2% decrease) and after 3 months (mean area decreased from 8.44 cm2 to 2.53 cm2, 70.0% decrease), with a mean monthly wound area reduction of 28.9%. The patients’ self-rated health on a vertical visual analogue scale also improved following the sequential therapy. The authors concluded that the sequential therapy is feasible option, with good wound healing and improvement in patients’ quality of life.
Guidelines from the Ministry of Health in Vietnam (2023) recommend polyabsorbent fibres with TLC-Ag dressings. They are described as “clinically effective in treating local infections and promoting wound healing” and “fast antibacterial with a broad spectrum and effective against biofilm”. The guidelines state: “polyabsorbent fibres keep the wound bed clean, optimising the effectiveness of silver ions at the wound bed.” TLC-NOSF dressings are recommended as “the first choice to significantly shorten ulcer healing time compared to other dressings, stressing out the cost-effectiveness of these dressings compared to other treatments.”
Aim
The authors were already using the two evaluated dressings based on their experience of clinical outcomes and integrated them in their standard of care. However, based on the above-mentioned papers, they aimed to evaluate the dressings as a sequential treatment to confirm/validate its effectiveness in the management of chronic wounds they encounter in their clinical practices in India. Six clinicians from different regions in India, with vast experience in managing DRUs and other chronic wounds authoring this paper, provide the results achieved in 10 challenging cases.
All patients consented to the evaluation of the sequential treatment. The wounds chosen were leg or foot ulcers in diabetic patients and a pressure injury with suspected clinical signs of local infection, and were followed-up till healing. This was a multicentre prospective evaluation to provide a representation of different settings in different regions of India.
Cases discussion
In cases 1 and 2, the clinician remarked that, after the application of polyabsorbent fibre dressing with TLC-Ag, there was a significant reduction in exudate and slough, and gradual improvement of granulation tissue. After a clean wound bed had been achieved, the treatment was shifted to a TLC-NOSF dressing which reduced the wound surface in a short period of time.
For cases 3 and 4, the application of polyabsorbent fibre dressing with TLC-Ag was associated with a significant reduction in exudate, slough, and continuous reduction in pain while an improvement of granulation tissue was evident. Once the infection subsided, the treatment switch to TLC-NOSF dressing led to a drastic wound area reduction and rapid closure of the wound, allowing a return to a more normal life for the patients.
In cases 5 and 6, the clinician emphasised the significant reduction in exudate levels and reduced pain scores after the application of the polyabsorbent fibre dressing with TLC-Ag dressing. After the application of TLC-NOSF dressing, there was a rapid reduction in wound surface area.
In cases 7 and 8, the clinician remarked that after the application of the polyabsorbent fibre dressing with TLC-Ag, there was a significant reduction in exudate levels, gradual improvement of granulation tissue and complete removal of slough, with reduced pain scores. Thereafter, the TLC-NOSF dressing rapidly improved the quality of granulation and facilitated a quick resolution of the wounds.
In cases 9 and 10, the clinician underlined that, after the application of polyabsorbent fibre with TLC-Ag dressing, there was a significant reduction in exudate levels, gradual improvement of granulation tissue and complete removal of the slough tissue, as well as a reduction of pain scores. After the application of a TLC-NOSF dressing, there was significant rapid wound closure, preventing any new adverse events or local infection episodes.
Pain scores in all these cases were based on the Numerical Rating Scale (Boonstra et al, 2016).
Discussion
DRUs are a serious and expensive complication of diabetes, and are a significant cause of mortality and morbidity, with added emotional distress, socioeconomic problems and low quality of life (Jalilian et al, 2020; Akkus and Sert, 2022). Managing a DRU requires good clinical care which incorporates adequate and frequent debridement/desloughing, offloading (when indicated), moist wound environment, treatment of infection and revascularisation for ischaemia when necessary (Kavitha et al, 2014). Wound healing can be enhanced by the appropriate choice of a dressing regime, which is a crucial step in the standard of care of these ulcers (Kavitha et al, 2014). Although there is a considerable range of dressing products available, robust evidence regarding the mode of action and effectiveness is available for only few dressings (Vowden and Vowden, 2017).
The evaluated dressings assessed as a sequential management protocol in the management of these cases, have robust supporting evidence, ranging from in vitro to in vivo clinical studies, including rare double-blind trials (Meaume et al, 2012a; Edmonds et al, 2018) and several real-life studies (Dissemond et al, 2020b; Gupta et al, 2021).
The polyabsorbent fibre dressing with TLC-Ag has been shown to effectively reduce slough and infection, and acts as an anti-biofilm (Dowsett, 2023). Moreover, the TLC-NOSF treatment range has been demonstrated to enhance wound closure, reduce healing times, and improve patients’ health-related quality of life, while also being cost-effective (Nair et al, 2021).
In this prospective evaluation, the choice of the clinicians to apply this sequential treatment was based on this wealth of evidence. These dressings have been already used as part of the evidence-based standard of care in their clinics and hospitals, and evaluating them as a sequential management of DRUs was a progression to strive to provide the best solutions for their patients.
The wounds with clinical signs of local infection were initial managed with the polyabsorbent fibre with TLC-Ag dressing, which rapidly resolved these symptoms. The move from the antimicrobial dressing to a TLC-NOSF dressing was done once these signs were resolved (on average after 4.9 weeks), while patients also benefited from a rapid reduction in sloughy tissue, exudate and pain.
Although the TLC-NOSF dressing was initiated as the second part of the sequential therapy, it was immediately initiated after the antimicrobial treatment. It should be noted that, in a pooled data analysis of 10,220 patients with chronic wounds, it was shown that the shortest time-to-closure was reached when wounds were treated with first-line TLC-NOSF dressings regardless of severity and nature of chronic wound (Munter et al, 2017).
Early closure of DRUs is considered crucial in order to prevent further complications, with Edmonds et al (2020) highlighting that “time is tissue”. Moreover, Hwang (2023) iterated that early treatment equals fewer complications and earlier healing.
Conclusion
The management of DRUs is always challenging. The authors have been managing these types of wounds for many years, but wanted to explore new local treatment strategies in the management of DRUs presenting with or suspicion of local clinical signs and symptoms of infection to get even better results. The evaluated dressings have robust evidence behind them and are also recommended by expert panels, boards and governmental entities.
The results achieved in all cases were satisfactory, with a rapid reduction of clinical signs of infection, slough, exudate and pain, and a rapid wound closure, with no adverse events reported during the course of treatment. The sequential treatment may help to reduce morbidity and mortality in patients with infected DRU by resolving these wounds in a shorter period.
